Janovska Petra, Bardova Kristina, Prouzova Zuzana, Irodenko Ilaria, Kobets Tatyana, Haasova Eliska, Steiner Mrazova Lenka, Stranecky Viktor, Kmoch Stanislav, Rossmeisl Martin, Zouhar Petr, Kopecky Jan
Laboratory of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czechia.
Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czechia.
Front Pediatr. 2025 May 20;13:1572836. doi: 10.3389/fped.2025.1572836. eCollection 2025.
During human foetal development, the liver is the primary site of blood cell production, but this activity declines in the third trimester and postnatally as haematopoiesis shifts to bone marrow. In humans, this postnatal decline is not well characterized due to the scarcity of appropriate samples.
To characterize the effect of (i) gestational age at birth and (ii) length of survival after birth on hepatic haematopoiesis across various cell lineages involved.
Liver autopsy samples from 25 born-alive infants, predominantly extremely preterm newborns who died mainly between 1 day and 3 weeks after birth, were analysed. Haematopoiesis was characterized using immunohistochemical staining of established cell type-specific protein markers. RNA-sequencing data from our previous study using the same samples were also explored.
Haematopoiesis negatively correlates with both the duration of prenatal development and the length of postnatal survival. The effect of these two factors varies across different haematopoietic cell lineages. Prenatally and early postnatally, erythropoietic cells dominated hepatic haematopoiesis but were rapidly suppressed within three days after birth. Granulopoietic activity declined more gradually after birth. Analysis of the gene expression data revealed the possible involvement of several transcription factors in lineage-specific regulatory mechanisms.
This study enhances our understanding of the postnatal decline of hepatic haematopoiesis in human newborns, highlighting the differential regulation of erythropoiesis and granulopoiesis after birth. These factors bring new in-depth knowledge about the biological processes critical for postnatal adaptation of human newborns.
在人类胎儿发育过程中，肝脏是血细胞生成的主要部位，但随着造血功能在妊娠晚期和出生后转移至骨髓，该活动会下降。在人类中，由于缺乏合适的样本，这种出生后的下降情况尚未得到充分表征。
表征（i）出生时的胎龄和（ii）出生后的存活时长对涉及的各种细胞谱系肝脏造血的影响。
分析了25例活产婴儿的肝脏尸检样本，主要是极早产儿，他们主要在出生后1天至3周内死亡。使用已建立的细胞类型特异性蛋白质标志物的免疫组织化学染色来表征造血情况。还探索了我们之前使用相同样本的研究中的RNA测序数据。
造血与产前发育时长和出生后存活时长均呈负相关。这两个因素的影响在不同造血细胞谱系中有所不同。在产前和出生后早期，红细胞生成细胞主导肝脏造血，但在出生后三天内迅速受到抑制。粒细胞生成活动在出生后下降得更为缓慢。对基因表达数据的分析揭示了几种转录因子可能参与谱系特异性调节机制。
本研究增进了我们对人类新生儿肝脏造血出生后下降的理解，突出了出生后红细胞生成和粒细胞生成的差异调节。这些因素为人类新生儿出生后适应的关键生物学过程带来了新的深入认识。
