Produção Nacional
Revisado por pares
Daily light and darkness onset and circadian rhythms metabolically synchronize hematopoietic stem cell differentiation and maintenance: The role of bone marrow norepinephrine, tumor necrosis factor, and melatonin cycles
2019; Elsevier BV; Volume: 78; Linguagem: Inglês
10.1016/j.exphem.2019.08.008
ISSN1873-2399
AutoresKarin Golan, Órit Kollet, Regina P. Markus, Tsvee Lapidot,
Tópico(s)Dietary Effects on Health
Resumo•Light/dark onset induces BM NE and TNF bursts, transiently upregulate ROS in HSPCs.•NE and TNF ROS bursts induce functionally distinct 11 AM and 11 PM HSPC peaks.•11 AM peak: HSPC differentiation and recruitment to replenish the blood.•11 PM melatonin peak: HSPC renewal, BM retention, and higher repopulation potential. Hematopoietic stem and progenitor cells (HSPCs) are essential for daily mature blood cell production, host immunity, and osteoclast-mediated bone turnover. The timing at which stem cells give rise to mature blood and immune cells while maintaining the bone marrow (BM) reservoir of undifferentiated HSPCs and how these opposite tasks are synchronized are poorly understood. Previous studies revealed that daily light onset activates norepinephrine (NE)-induced BM CXCL12 downregulation, followed by CXCR4+ HSPC release to the circulation. Recently, we reported that daily light onset induces transient elevations of BM NE and tumor necrosis factor (TNF), which metabolically program BM HSPC differentiation and recruitment to replenish the blood. In contrast, darkness onset induces lower elevations of BM NE and TNF, activating melatonin production, which metabolically reprograms HSPCs, increasing their short- and long-term repopulation potential, and BM maintenance. How the functions of BM-retained HSPCs are influenced by daily light and darkness cycles and their clinical potential are further discussed. Hematopoietic stem and progenitor cells (HSPCs) are essential for daily mature blood cell production, host immunity, and osteoclast-mediated bone turnover. The timing at which stem cells give rise to mature blood and immune cells while maintaining the bone marrow (BM) reservoir of undifferentiated HSPCs and how these opposite tasks are synchronized are poorly understood. Previous studies revealed that daily light onset activates norepinephrine (NE)-induced BM CXCL12 downregulation, followed by CXCR4+ HSPC release to the circulation. Recently, we reported that daily light onset induces transient elevations of BM NE and tumor necrosis factor (TNF), which metabolically program BM HSPC differentiation and recruitment to replenish the blood. In contrast, darkness onset induces lower elevations of BM NE and TNF, activating melatonin production, which metabolically reprograms HSPCs, increasing their short- and long-term repopulation potential, and BM maintenance. How the functions of BM-retained HSPCs are influenced by daily light and darkness cycles and their clinical potential are further discussed. Hematopoietic stem and progenitor cells (HSPCs) dynamically replenish the blood with new mature blood and immune cells with a finite life span, while maintaining and renewing the undifferentiated HSPC bone marrow (BM) reservoir. Long-term repopulating hematopoietic stem cells (LT-HSCs) are identified and characterized in preclinical experimental transplantation assays, based on their functional ability to home and to durably repopulate the BM and blood with high levels of both myeloid and lymphoid cells. Short-term repopulating HSPCs are metabolically active with high levels of reactive oxygen species (ROShigh), giving rise to myeloid-biased differentiation and repopulation, while LT-HSCs are mostly retained in the BM in a nonmotile, quiescent, low-reactive-oxygen-species (ROSlow) metabolic state [1Ludin A Gur-Cohen S Golan K et al.Reactive oxygen species regulate hematopoietic stem cell self-renewal, migration and development, as well as their bone marrow microenvironment.Antioxid Redox Signal. 2014; 21: 1605-1619Crossref PubMed Scopus (100) Google Scholar,2Suda T Takubo K Semenza GL Metabolic regulation of hematopoietic stem cells in the hypoxic niche.Cell Stem Cell. 2011; 9: 298-310Abstract Full Text Full Text PDF PubMed Scopus (415) Google Scholar]. These low metabolic features are induced by adhesion interactions with niche-supporting CXCL12+ BM stromal cells, which metabolically protect quiescent, CXCR4+/EPCR+, reserved LT-HSCs from DNA-damaging agents including radiation and chemotherapy insult, which preferentially kill cycling cells [1Ludin A Gur-Cohen S Golan K et al.Reactive oxygen species regulate hematopoietic stem cell self-renewal, migration and development, as well as their bone marrow microenvironment.Antioxid Redox Signal. 2014; 21: 1605-1619Crossref PubMed Scopus (100) Google Scholar,3Sugiyama T Kohara H Noda M Nagasawa T Maintenance of the hematopoietic stem cell pool by CXCL12–CXCR4 chemokine signaling in bone marrow stromal cell niches.Immunity. 2006; 25: 977-988Abstract Full Text Full Text PDF PubMed Scopus (1321) Google Scholar, 4Gur-Cohen S Itkin T Chakrabarty S et al.PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells.Nat Med. 2015; 21: 1307-1317Crossref PubMed Google Scholar, 5Tzeng YS Li H Kang YL Chen WC Cheng WC Lai DM Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the pattern of hematopoietic regeneration after myelosuppression.Blood. 2011; 117: 429-439Crossref PubMed Scopus (157) Google Scholar, 6Zhao M Tao F Venkatraman A et al.N-Cadherin-expressing bone and marrow stromal progenitor cells maintain reserve hematopoietic stem cells.Cell Rep. 2019; 26 (652–669.e656)Abstract Full Text Full Text PDF Scopus (5) Google Scholar]. Chemotherapy-resistant CD73-expressing BM mesenchymal stem cells (MSCs) are spatially located at the endosteum and bone fraction, being pivotal for BM engraftment and hematopoietic recovery [7Severe N Karabacak NM Gustafsson K et al.Stress-induced changes in bone marrow stromal cell populations revealed through single-cell protein expression mapping.Cell Stem Cell. 2019; https://doi.org/10.1016/j.stem.2019.06.003Abstract Full Text Full Text PDF PubMed Google Scholar]. In line, chemotherapy-resistant LT-HSCs (reserved) are mainly maintained in the endosteum [6Zhao M Tao F Venkatraman A et al.N-Cadherin-expressing bone and marrow stromal progenitor cells maintain reserve hematopoietic stem cells.Cell Rep. 2019; 26 (652–669.e656)Abstract Full Text Full Text PDF Scopus (5) Google Scholar]. The chemotherapy resistance of BM LT-HSCs involves excess ROS transfer from chemotherapy-activated hematopoietic stem cells to their niche-supporting BM stromal cells [8Taniguchi Ishikawa E Gonzalez-Nieto D Ghiaur G et al.Connexin-43 prevents hematopoietic stem cell senescence through transfer of reactive oxygen species to bone marrow stromal cells.Proc Natl Acad Sci USA. 2012; 109: 9071-9076Crossref PubMed Scopus (75) Google Scholar]. Our preliminary results suggest that this ROS transfer is actually due to mitochondria transfer [9Golan K Wellendorf A Takihara Y et al.Mitochondria transfer from hematopoietic stem and progenitor cells to Pdgfrα+/Sca1–/CD48dim BM stromal cells via CX43 gap junctions and AMPK signaling inversely regulate ROS generation in both cell populations.Blood. 2016; 128: 5Crossref PubMed Google Scholar]. Several studies revealed that BM-retained primitive LT-HSCs are dormant, hibernating, quiescent stem cells, which rarely engage in cell cycle and make only minor contributions to hematopoiesis during steady-state homeostasis [10Cabezas-Wallscheid N Buettner F Sommerkamp P et al.Vitamin A–retinoic acid signaling regulates hematopoietic stem cell dormancy.Cell. 2017; 169 (807–823.e819)Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 11Morrison SJ Scadden DT The bone marrow niche for haematopoietic stem cells.Nature. 2014; 505: 327-334Crossref PubMed Scopus (1010) Google Scholar, 12Wilson A Laurenti E Trumpp A Balancing dormant and self-renewing hematopoietic stem cells.Curr Opin Genet Dev. 2009; 19: 461-468Crossref PubMed Scopus (137) Google Scholar, 13Yamazaki S Iwama A Takayanagi S et al.Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells.EMBO J. 2006; 25: 3515-3523Crossref PubMed Scopus (189) Google Scholar, 14Sun J Ramos A Chapman B et al.Clonal dynamics of native haematopoiesis.Nature. 2014; 514: 322-327Crossref PubMed Scopus (353) Google Scholar]. In contrast, other studies have found that some LT-HSCs also actively participate in steady-state hematopoiesis and durably contribute to multilineage cell production [15Sawai CM Babovic S Upadhaya S et al.Hematopoietic stem cells are the major source of multilineage hematopoiesis in adult animals.Immunity. 2016; 45: 597-609Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 16Sawen P Eldeeb M Erlandsson E et al.Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging.Elife. 2018; 7Crossref PubMed Scopus (5) Google Scholar, 17Chapple RH Tseng YJ Hu T et al.Lineage tracing of murine adult hematopoietic stem cells reveals active contribution to steady-state hematopoiesis.Blood Adv. 2018; 2: 1220-1228Crossref PubMed Scopus (10) Google Scholar]. Future studies will resolve this controversy and will reveal how and when LT-HSCs play an active role in replenishing the circulation. The most primitive BM-retained LT-HSCs play a major role in durable long-term repopulation following BM transplantation. These primitive, quiescent HSCs are rapidly activated during alarm situations caused by infections, injury, bleeding, and DNA damage, to prevent lethal hematology and immune failure. We therefore hypothesize that their need to be immediately and ongoing ready for activation on demand during alarm situations requires their daily dynamic metabolic "exercise and training" circadian rhythms. These are induced by light and darkness onset also independently of cell division. BM-retained, quiescent HSCs are maintained undifferentiated until they are activated by local signals originating from the stem cell niche microenvironment and by bone-degrading osteoclast activity [18Kollet O Dar A Shivtiel S et al.Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells.Nat Med. 2006; 12: 657-664Crossref PubMed Scopus (556) Google Scholar]. Other cues activating HSCs are peripheral signals originating from the nervous, immune, and hemostatic systems [19Mendez-Ferrer S Chow A Merad M Frenette PS Circadian rhythms influence hematopoietic stem cells.Curr Opin Hematol. 2009; 16: 235-242Crossref PubMed Scopus (0) Google Scholar, 20King KY Goodell MA Inflammatory modulation of HSCs: Viewing the HSC as a foundation for the immune response.Nat Rev Immunol. 2011; 11: 685-692Crossref PubMed Scopus (258) Google Scholar, 21Nguyen TS Lapidot T Ruf W Extravascular coagulation in hematopoietic stem and progenitor cell regulation.Blood. 2018; 132: 123-131Crossref PubMed Scopus (4) Google Scholar]. Leukocyte trafficking and BM HSPC maintenance are also regulated by distinct BM blood vessel types, with the less permeable arterioles and capillaries, maintaining primitive HSPCs in an ROSlow state, whereas the more permeable sinusoids predominantly promote ROShigh HSPC activation and trafficking [22Itkin T Gur-Cohen S Spencer JA et al.Distinct bone marrow blood vessels differentially regulate haematopoiesis.Nature. 2016; 532: 323-328Crossref PubMed Google Scholar,23Kusumbe AP Ramasamy SK Itkin T et al.Age-dependent modulation of vascular niches for haematopoietic stem cells.Nature. 2016; 532: 380-384Crossref PubMed Google Scholar]. In line, BM imaging showed that quiescent HSCs preferentially localize near endosteal arterioles [24Kunisaki Y Bruns I Scheiermann C et al.Arteriolar niches maintain haematopoietic stem cell quiescence.Nature. 2013; 502: 637-643Crossref PubMed Scopus (542) Google Scholar]. Bone cavities are formed by osteoclast-mediated bone turnover and are another component of the HSC niche microenvironment. Osteoclast activity also promotes HSPC mobilization, and osteopetrotic mice lacking bone cavities because of defective osteoclasts are not protected from chemotherapy insult. As a result, these mice rapidly die following chemotherapy treatment, which kills cycling cells [18Kollet O Dar A Shivtiel S et al.Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells.Nat Med. 2006; 12: 657-664Crossref PubMed Scopus (556) Google Scholar,25Miyamoto K Yoshida S Kawasumi M et al.Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization.J Exp Med. 2011; 208: 2175-2181Crossref PubMed Scopus (0) Google Scholar]. Peripheral signals leading to neurotransmitter secretion in the BM regulate mature leukocytes as well as immature HSPCs. Inhibition of the sympathetic nervous system (SNS) resulted in increased myelopoiesis and reduced lymphopoiesis following BM transplantation [26Maestroni GJ Conti A Pedrinis E Effect of adrenergic agents on hematopoiesis after syngeneic bone marrow transplantation in mice.Blood. 1992; 80: 1178-1182PubMed Google Scholar]. Norepinephrine, the sympathetic neurotransmitter, rescued hematopoiesis and mouse survival following chemotherapy and irradiation [27Maestroni GJ Togni M Covacci V Norepinephrine protects mice from acute lethal doses of carboplatin.Exp Hematol. 1997; 25: 491-494PubMed Google Scholar]. In addition, both human and murine HSPCs functionally express dopamine and B2 adrenergic receptors with higher levels of expression in the more primitive human CD34+/CD38– stem cells [28Spiegel A Shivtiel S Kalinkovich A et al.Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling.Nat Immunol. 2007; 8: 1123-1131Crossref PubMed Scopus (221) Google Scholar]. Adrenergic signals regulate human and murine HSPC retention, egress, and mobilization via direct and indirect effects through the BM microenvironment [19Mendez-Ferrer S Chow A Merad M Frenette PS Circadian rhythms influence hematopoietic stem cells.Curr Opin Hematol. 2009; 16: 235-242Crossref PubMed Scopus (0) Google Scholar,28Spiegel A Shivtiel S Kalinkovich A et al.Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling.Nat Immunol. 2007; 8: 1123-1131Crossref PubMed Scopus (221) Google Scholar, 29Katayama Y Battista M Kao WM et al.Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow.Cell. 2006; 124: 407-421Abstract Full Text Full Text PDF PubMed Scopus (830) Google Scholar, 30Dar A Schajnovitz A Lapid K et al.Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells.Leukemia. 2011; 25: 1286-1296Crossref PubMed Scopus (135) Google Scholar]. Nonmyelinating Schwann cells are hematopoietic niche glial cells ensheathed by autonomic nerves, which induce HSC quiescence via transforming growth factor (TGF)-β activation and signaling [31Yamazaki S Ema H Karlsson G et al.Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche.Cell. 2011; 147: 1146-1158Abstract Full Text Full Text PDF PubMed Scopus (418) Google Scholar]. Interestingly these stem cell niche nerve cells are also shielded from the ROShigh circulating blood cells and are located near bone and the less permeable BM blood vessels, most probably because of their ROS sensitivity [22Itkin T Gur-Cohen S Spencer JA et al.Distinct bone marrow blood vessels differentially regulate haematopoiesis.Nature. 2016; 532: 323-328Crossref PubMed Google Scholar]. Osteoclast activity involves TGF-β activation via its release from the degraded bone, which in turn recruits Sca-1+ bone-forming osteoblast precursors to the bone remodeling cite [32Wu X Pang L Lei W et al.Inhibition of Sca-1-positive skeletal stem cell recruitment by alendronate blunts the anabolic effects of parathyroid hormone on bone remodeling.Cell Stem Cell. 2010; 7: 571-580Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar]. Human bone metabolism, including bone remodeling, is regulated by the SNS, thus affecting HSPC maintenance, trafficking, and blood replenishment [33Khosla S Drake MT Volkman TL et al.Sympathetic beta1-adrenergic signaling contributes to regulation of human bone metabolism.J Clin Invest. 2018; 128: 4832-4842Crossref PubMed Scopus (0) Google Scholar,34Hofbauer LC Henneicke H beta-Blockers and bone health.J Clin Invest. 2018; 128: 4745-4747Crossref PubMed Scopus (0) Google Scholar]. The dynamic and complex interplay between the hemostatic, immune and nervous systems, bone remodeling (osteoblasts and osteoclasts), and the BM microenvironment regulate both blood and immune cell production as well as bone turnover [19Mendez-Ferrer S Chow A Merad M Frenette PS Circadian rhythms influence hematopoietic stem cells.Curr Opin Hematol. 2009; 16: 235-242Crossref PubMed Scopus (0) Google Scholar,21Nguyen TS Lapidot T Ruf W Extravascular coagulation in hematopoietic stem and progenitor cell regulation.Blood. 2018; 132: 123-131Crossref PubMed Scopus (4) Google Scholar,35Gur-Cohen S Kollet O Graf C Esmon CT Ruf W Lapidot T Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling.Ann NY Acad Sci. 2016; 1370: 65-81Crossref PubMed Scopus (11) Google Scholar,36Ramasamy SK Kusumbe AP Itkin T Gur-Cohen S Lapidot T Adams RH Regulation of hematopoiesis and osteogenesis by blood vessel-derived signals.Annu Rev Cell Dev Biol. 2016; 32: 649-675Crossref PubMed Scopus (33) Google Scholar]. An important and essential regulator of the body is melatonin, the darkness hormone. Melatonin is produced in the pineal gland during darkness and is evolutionarily conserved and found in almost all living organisms [37Amaral FGD Cipolla-Neto J A brief review about melatonin, a pineal hormone.Arch Endocrinol Metab. 2018; 62: 472-479Crossref PubMed Scopus (5) Google Scholar]. Its pineal synthesis is timed by the suprachiasmatic nucleus (SCN) via nocturnal sympathetic input via noradrenaline and ATP activation of β2 adrenoceptors and P2Y1 purinergic receptors, respectively. The production of the darkness hormone is negatively regulated by the pro-inflammatory cytokines and pathogen-associated molecular patterns via NF-κB in pinealocytes, and positively regulated in monocytes/macrophages and dendritic cells [38Muxel SM Laranjeira-Silva MF Carvalho-Sousa CE Floeter-Winter LM Markus RP The RelA/cRel nuclear factor-kappaB (NF-kappaB) dimer, crucial for inflammation resolution, mediates the transcription of the key enzyme in melatonin synthesis in RAW 264.7 macrophages.J Pineal Res. 2016; 60: 394-404Crossref PubMed Scopus (25) Google Scholar, 39Fernandes PA Tamura EK D'Argenio-Garcia L et al.Dual effect of catecholamines and corticosterone crosstalk on pineal gland melatonin synthesis.Neuroendocrinology. 2017; 104: 126-134Crossref PubMed Scopus (11) Google Scholar, 40Markus RP Fernandes PA Kinker GS da Silveira Cruz-Machado S Marcola M Immune-pineal axis-acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes.Br J Pharmacol. 2018; 175: 3239-3250Crossref PubMed Scopus (12) Google Scholar]. Melatonin regulates circadian rhythms, body temperature cycles, and immune responses, and is involved in different pathological disorders including cancer and cardiovascular diseases [41Tordjman S Chokron S Delorme R et al.Melatonin: Pharmacology, functions and therapeutic benefits.Curr Neuropharmacol. 2017; 15: 434-443Crossref PubMed Scopus (18) Google Scholar,42Carrillo-Vico A Lardone PJ Alvarez-Sanchez N Rodriguez-Rodriguez A Guerrero JM Melatonin: buffering the immune system.Int J Mol Sci. 2013; 14: 8638-8683Crossref PubMed Scopus (269) Google Scholar]. Interestingly, extra-pineal production of melatonin has been reported for different cells including myeloid cells [43Pires-Lapa MA Carvalho-Sousa CE Cecon E Fernandes PA Markus RP Beta-adrenoceptors trigger melatonin synthesis in phagocytes.Int J Mol Sci. 2018; 19Crossref PubMed Scopus (5) Google Scholar]. In the human and murine BM, there is also local production of melatonin by bone-forming stromal precursors, and preconditioning of mesenchymal cells with melatonin increases their survival and therapeutic efficiency [44Conti A Conconi S Hertens E Skwarlo-Sonta K Markowska M Maestroni JM Evidence for melatonin synthesis in mouse and human bone marrow cells.J Pineal Res. 2000; 28: 193-202Crossref PubMed Google Scholar, 45Mias C Trouche E Seguelas MH et al.Ex vivo pretreatment with melatonin improves survival, proangiogenic/mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney.Stem Cells. 2008; 26: 1749-1757Crossref PubMed Scopus (0) Google Scholar, 46Tan DX Manchester LC Reiter RJ et al.Identification of highly elevated levels of melatonin in bone marrow: Its origin and significance.Biochim Biophys Acta. 1999; 1472: 206-214Crossref PubMed Scopus (271) Google Scholar]. The facts that melatonin can be locally secreted in the BM and melatonin receptors are expressed on leukocytes as well as on BM stromal cells suggest that melatonin may play a role in BM stem cell regulation. As both the SNS and melatonin undergo daily regulation by light and darkness, and BM CXCR4+ HSPC release and their niche supporting chemokine CXCL12 also undergo circadian rhythms [47Mendez-Ferrer S Lucas D Battista M Frenette PS Haematopoietic stem cell release is regulated by circadian oscillations.Nature. 2008; 452: 442-447Crossref PubMed Scopus (713) Google Scholar,48Lucas D Battista M Shi PA Isola L Frenette PS Mobilized hematopoietic stem cell yield depends on species-specific circadian timing.Cell Stem Cell. 2008; 3: 364-366Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar], we investigated the potential role of all these factors in the physiological daily regulation of BM HSPC function and maintenance. This review, overviews recent advances in the light of previous insights, to provide an updated and current understanding of how daily light and darkness onset and circadian rhythms regulate BM HSC differentiation and maintenance. Physiological and biological functions of all mammals are regulated by the changing surrounding environmental cues, and in particular daily light and darkness cycles, which are defined as circadian rhythms. Adjustment to light/dark cycles is governed by the brain pacemaker, the SCN, which daily synchronizes peripheral organs via the autonomous nervous system [19Mendez-Ferrer S Chow A Merad M Frenette PS Circadian rhythms influence hematopoietic stem cells.Curr Opin Hematol. 2009; 16: 235-242Crossref PubMed Scopus (0) Google Scholar]. One of the peripheral organs regulated by light/darkness cues is the BM, the major origin of adult hematopoiesis. Hematopoiesis and host immunity follow daily rhythms in cell proliferation and function including BM production of blood cells and various leukocytes, which were all augmented during daytime both in humans and in mice [49Halberg F Johnson EA Brown BW Bittner JJ Susceptibility rhythm to E.coli endotoxin and bioassay. Proc Soc Exp Biol Med. 1960; 103: 142-144Crossref PubMed Google Scholar, 50Abrahamsen JF Smaaland R Sothern RB Laerum OD Circadian cell cycle variations of erythro- and myelopoiesis in humans.Eur J Haematol. 1997; 58: 333-345Crossref PubMed Google Scholar, 51Aardal NP. Circannual variations of circadian periodicity in murine colony-forming cells.Exp Hematol. 1984; 12: 61-67PubMed Google Scholar, 52Wood PA Hrushesky WJ Klevecz R Distinct circadian time structures characterize myeloid and erythroid progenitor and multipotential cell clonogenicity as well as marrow precursor proliferation dynamics.Exp Hematol. 1998; 26: 523-533PubMed Google Scholar, 53Sharkis SJ Palmer JD Goodenough J LoBue J Gordon AS Daily variation of marrow and splenic erythropoiesis, pinna epidermal cell mitosis and physical activity in C57B1-6J mice.Cell Tissue Kinet. 1974; 7: 381-387PubMed Google Scholar, 54Baudoux E Beguin Y Cornu G et al.Circadian and seasonal variations of hematopoiesis in cord blood.Bone Marrow Transplant. 1998; 22: S12PubMed Google Scholar, 55Pick R He W Chen CS Scheiermann C Time-of-day-dependent trafficking and function of leukocyte subsets.Trends Immunol. 2019; 40: 524-537Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar]. Mature neutrophil turnover in mice is also regulated by circadian rhythms [56Casanova-Acebes M Pitaval C Weiss LA et al.Rhythmic modulation of the hematopoietic niche through neutrophil clearance.Cell. 2013; 153: 1025-1035Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar,57Weger M Diotel N Dorsemans AC Dickmeis T Weger BD Stem cells and the circadian clock.Dev Biol. 2017; 431: 111-123Crossref PubMed Scopus (24) Google Scholar]. Homeostatic leukocyte recruitment to different organs exhibits circadian oscillations orchestrated by adrenergic nerves [58Scheiermann C Kunisaki Y Lucas D et al.Adrenergic nerves govern circadian leukocyte recruitment to tissues.Immunity. 2012; 37: 290-301Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar], and variations in transplanted BM cell engraftment potential were observed upon changes in time of transplantation [59D'Hondt L McAuliffe C Damon J et al.Circadian variations of bone marrow engraftability.J Cell Physiol. 2004; 200: 63-70Crossref PubMed Scopus (0) Google Scholar,60Muller WA Regulate globally, act locally: Adrenergic nerves promote leukocyte recruitment.Immunity. 2012; 37: 189-191Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]. Not only the BM compartment undergoes circadian variations but also the profile of circulating blood cells. Circulating human myeloid progenitor cells, polymorphonuclear (PMN) leukocytes, and endothelial progenitors demonstrate diurnal variations, with higher levels during the day [61Ross DD Pollak A Akman SA Bachur NR Diurnal variation of circulating human myeloid progenitor cells.Exp Hematol. 1980; 8: 954-960PubMed Google Scholar, 62Verma DS Fisher R Spitzer G Zander AR McCredie KB Dicke KA Diurnal changes in circulating myeloid progenitor cells in man.Am J Hematol. 1980; 9: 185-192Crossref PubMed Scopus (0) Google Scholar, 63Thomas HE Redgrave R Cunnington MS Avery P Keavney BD Arthur HM Circulating endothelial progenitor cells exhibit diurnal variation.Arterioscler Thromb Vasc Biol. 2008; 28: e21-e22Crossref PubMed Scopus (33) Google Scholar, 64Morra L Ponassi A Caristo G et al.Comparison between diurnal changes and changes induced by hydrocortisone and epinephrine in circulating myeloid progenitor cells (CFU-GM) in man.Biomed Pharmacother. 1984; 38: 167-170PubMed Google Scholar]. Interestingly, daily HSPC release and the yield of G-CSF mobilized PBL follow circadian rhythms [47Mendez-Ferrer S Lucas D Battista M Frenette PS Haematopoietic stem cell release is regulated by circadian oscillations.Nature. 2008; 452: 442-447Crossref PubMed Scopus (713) Google Scholar,48Lucas D Battista M Shi PA Isola L Frenette PS Mobilized hematopoietic stem cell yield depends on species-specific circadian timing.Cell Stem Cell. 2008; 3: 364-366Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar]. The highest levels of mouse and human circulating HSPC are found in the resting phase, morning for mice and night for humans [48Lucas D Battista M Shi PA Isola L Frenette PS Mobilized hematopoietic stem cell yield depends on species-specific circadian timing.Cell Stem Cell. 2008; 3: 364-366Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar,65Shi PA Isola LM Gabrilove JL et al.Prospective cohort study of the circadian rhythm pattern in allogeneic sibling donors undergoing standard granulocyte colony-stimulating factor mobilization.Stem Cell Res Ther. 2013; 4: 30Crossref PubMed Scopus (0) Google Scholar]. Recently, by applying functional, preclinical murine stem cell models, we revealed that light onset and darkness onset differentially regulate BM HSPC differentiation and blood replenishment, while maintaining the BM reservoir of undifferentiated LT-HSCs. We identified two daily peaks in the levels of BM HSPCs, one 5 hours following light initiation and the other, 5 hours following darkness onset. Deeper investigations revealed that the morning peak involves differentiation, migration, increased vascular permeability, egress, and blood replenishment. The night peak involves decreased BM vascular permeability and renewal of the BM LT-HSC reservoir. The levels and BM repopulation potential of HSPC are elevated during the night (Figure 1). Overall, the two major HSPC peaks are phenotypically and functionally different [66Golan K Kumari A Kollet O et al.Daily onset of light and darkness differentially controls hematopoietic stem cell differentiation and maintenance.Cell Stem Cell. 2018; 23 (572–585.e577)Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar]. The fluctuations observed in BM HSPC repopulation potential, including short-term and long-term repopulating HSCs, between day and night cannot be explained solely by increased proliferation. Our data suggest that BM HSPCs are metabolically primed by light and darkness cues that dynamically change their phenotype and function, as reflected by dynamic changes in cell surface receptor expression, for example, increased surface expression of the LT-HSC SLAM marker CD150 and reduced expression of c-Kit at night [66Golan K Kumari A Kollet O et al.Daily onset of light and darkness differentially controls hematopoietic stem cell differentiation and maintenance.Cell Stem Cell. 2018; 23 (572–585.e577)Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar]. In line, previous reports showed reduced c-Kit expression by LT-HSCs, while HSCs with higher c-Kit expression display more limited expansion capacities and have impaired self-renewal and major reductions in their repopulation potential [67Grinenko T Arndt K Portz M et al.Clonal expansion capacity defines two consecutive deve
Referência(s)